Heavy tobacco users, otherwise without drug abuse histories, were studied on the Residential Research Unit. In the withdrawal study, subjects were assessed for nicotine and cotinine, general cardiovascular functioning, passive EEG and evoked cortical potential, and caloric intake, during 10 days of cigarette deprivation and when smoking resumed. In the substitution phase of the study, subjects were tested during alternating cycles of 4 days smoking and 3 days abstinence. In this phase, subjects were similarly assessed as described above, but on days in which they were not permitted to smoke, they were given pieces of gum to chew 12 times per day at one hour intervals: the gum contained either 0, 2 or 4 mg of nicotine. We found that an orderly withdrawal emerged. It included impaired performance, which did not recover within the ten days of abstinence, but did recover when cigarette smoking resumed. Nicotine gum reversed major signs of tobacco withdrawal, confirming that the withdrawal was nicotine specific. This effect was dose-related, e.g., 4 mg gum restored performance to baseline levels, whereas 2 mg gum only partially restored performance. Placebo gum use was accompanied by withdrawal. Together, these results confirm that nicotine replacement can be a viable mode of alleviation of the tobacco withdrawal syndrome, but is of little benefit in reducing desire to smoke (which appears to by pharmaccologically related to abstinence but appears readily elicited by environmental stimuli).